We propose to examine the quantitative response of specific spermatogenic cells to defined changes in testosterone concentration within the seminiferous tubules of the adult rat. Two specific aims are proposed. The first is to determine the effect on germ cell numbers per testis of clamping intratubular testosterone concentrations at levels below those normally present in the tubules of control rats. To this end, experiments are proposed that are designed to show: 1) whether the production of advanced spermatids by the adult rat testis can be maintained quantitatively at intratubular testosterone concentrations that are clamped below the concentrations found in the tubules of control rats; 2) Whether the same minimum intratubular testosterone concentration is required to maintain normal numbers of advanced spermatids per testis in rats with, and deprived of, endogenous FSH; and 3) whether and when specific spermatogenic cell types change in number per testis in response to a series of defined step reductions in intratubular testosterone concentration. The second specific aim is to determine the quantitative effect of reduced intratubular testosterone concentrations on the number of specific germ cells per testis at particular stages of the cycle of the seminiferous epithelium. To this end, rats whose testes have been synchronized at particular stages of the cycle of the seminiferous epithelium will be used to show: 1) whether there are significant differences in intratubular testosterone concentrations at different stages of the cycle; 2) whether the maintenance of normal numbers of specific spermatogenic cell types at different stages requires different intratubular testosterone concentrations; 3) whether there are stage-specific changes in the number of specific germ cells in response to changes in their intratubular testosterone environments; and 4) whether Leydig cell structure/function and androgen receptor concentrations are related to intratubular testosterone concentrations at different stages of the cycle. The results of these studies should substantially increase our understanding of the quantitative response of specific spermatogenic cells to changes in the hormonal milieu to which they are exposed. This information should increase our understanding of how spermatogenesis is regulated.